We will determine whether smoke from marijuana cigarettes has the same immediate deleterious effects on vascular endothelial vasodilatory function as those that are known to occur from exposure to tobacco smoke. One of the most pervasive, yet unsubstantiated, public beliefs surrounding marijuana smoking is that its effects on its smokers and bystanders alike are benign relative to the effects of tobacco. We and others have shown that exposure to tobacco SHS for 30 minutes causes substantial impairment of vasodilatory function in both humans and rats, as determined by ultrasound measurement of arterial flow-mediated vasodilation (FMD), a measure of endothelial health. This laboratory has developed a living rat FMD system that we are using to study the harmful effects of tobacco SHS. We will use this rat system both to be able to measure the effects of marijuana SHS in multiple individuals with very similar genetics and lifestyle, and to avoid the legal issues associated with exposing humans to this controlled substance. We wil also determine if exposure to marijuana mainstream smoke or SHS lowers NO production in cultured endothelial cells. We hypothesize that exposure to smoke from smoldering dried leaves, whether tobaco or marijuana and regardless of the presence of marijuana!s psychoactive component, causes impairment of vascular function. The demonstration that this is the case would have the impact of countering the common public misperception that environmental exposure to marijuana smoke is relatively harmless. Because of marijuana!s increasing use for medicinal purposes, and efforts underway in places like California to legalize marijuana, not to mention the undeniable fact that marijuana non-smokers are still exposed to its secondhand smoke in various situations, it is important to understand the public health effects of environmental exposure to this smoke. First, we will determine whether FMD is impaired in rats exposed to high and low levels of marijuana SHS, for exposure times ranging from 30 minutes down to a brief 30-second exposure, compared to the effects of tobacco SHS and other controls. Then, we will determine whether serum from rats that have been exposed to marijuana mainstream smoke or SHS lowers eNOS activity and NO production in cultured endothelial cells. PUBLIC HEALTH RELEVANCE: Many in the general public, even those who avoid tobacco smoke, believe that exposure to marijuana smoke is relatively harmless. We will determine whether smoke from marijuana cigarettes has the same immediate harmful efects on the cardiovascular system as those that are known to occur from exposure to tobacco secondhand smoke. Because of marijuana!s increasing use for medicinal purposes, and efforts underway in places like California to legalize marijuana, not to mention the undeniable fact that marijuana non- smokers are still exposed to its secondhand smoke in various situations, it is important to understand the public health effects of environmental exposure to this smoke.